Dysregulated germinal center reaction with expanded T follicular helper cells in autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy lymph nodes - 03/05/24
, Joona Sarkkinen, MD a, Nelli Heikkilä, MD, PhD a, Karen Drechsel, MSc a, Mikko I. Mäyränpää, MD, PhD b, Anniina Färkkilä, MD, PhD c, d, e, Saila Laakso, MD, PhD f, g, h, Outi Mäkitie, MD, PhD f, g, h, i, T. Petteri Arstila, MD, PhD a, Eliisa Kekäläinen, MD PhD aAbstract |
Background |
Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED, also called APS-1) is an inborn error of immunity with clear signs of B-cell autoimmunity such as neutralizing anti-IFN antibodies. In APECED, mutations in the AIRE gene impair thymic negative selection of T cells. The resulting T-cell alterations may then cause dysregulation of B-cell responses. However, no analysis of interactions of T and B cells in the germinal centers (GCs) in patients’ secondary lymphatic tissues has been reported.
Objective |
This study examined the relationship between B cells and follicular T helper cells (TfH) in peripheral blood and lymph node (LN) GCs in patients with APECED.
Methods |
Immunophenotyping of peripheral blood B cells and TfH was performed for 24 patients with APECED. Highly multiplexed fluorescent immunohistochemical staining was performed on 7 LN biopsy samples from the patients to study spatial interactions of lymphocytes in the GCs at the single-cell level.
Results |
The patients’ peripheral B-cell phenotype revealed skewing toward a mature B-cell phenotype with marked loss of transitional and naive B cells. The frequency of circulating TfH cells was diminished in the patients, while in the LNs the TfH population was expanded. In LNs the overall frequency of Treg cells and interactions of Treg cells with nonfollicular T cells were reduced, suggesting that aberrant Treg cell function might fail to restrain TfH differentiation.
Conclusions |
GC reactions are disrupted in APECED as a result of defective T-cell control.
Le texte complet de cet article est disponible en PDF.Key words : AIRE, autoantibody, inborn error of immunity, regulatory T cell, follicular regulatory T cell, follicular T helper cell, B cell
Abbreviations used : AIRE, APECED, APRIL, BAFF, cTfH, CTLA4, CXCR, es, FFPE, GC, LN, PD-1, TfH, TfR, Tnonf, Treg
Plan
| The last 2 authors contributed equally to this article, and both should be considered senior author. |
Vol 153 - N° 5
P. 1445-1455 - mai 2024 Retour au numéro
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